Cell growth is regulated by balance between the growth promoting mechanism and growth inhibitory mechanism. It is considered that at the time of growth, the promoting mechanism is superior to the inhibitory mechanism, and at the time of growth inhibition, the inhibitory mechanism is superior to the promoting mechanism. In normal cells, this balance is maintained suitably and a typical example is a wound-healing process. For example, if epithelial tissues are damaged, the growth promoting mechanism initiates proliferation and migration of cells to compensate for the damaged site, and when the damaged site is filled up, the growth inhibitory mechanism terminates the growth of the cells. In tumor cells, on the other hand, it is considered that the balance in growth control is lost by abnormal activation of the promoting mechanism or by inactivation of the inhibitory mechanism to permit uncontrollable self-growth of cells. By the advance of recent molecular biology and cell biology, molecules involved in controlling the growth of cells have been revealed, but there are not so many reports on the growth inhibitory and arrest mechanisms as compared with studies on the growth promoting mechanism. Recently, studies on the growth inhibitory mechanisms have been conducted extensively from the viewpoint of controlling cell cycle by tumor-suppression genes, G.sub.1 cyclin, cyclin-dependent kinase (CDK), inhibitory factor of CDK etc, but initial stimuli are still not known at the induction of growth arrest.
Known cell growth inhibitory factors having the activity of inhibiting growth of tumor cells include transforming growth factor (TGF)-.beta. which inhibits the growth of lung cancer cells [Proc. Natl. Acad. Sci. USA, 82, 119-123 (1985)] and epidermal growth factor (EGF) which inhibits the growth of squamous carcinoma cells [Nature, 293, 305-307 (1981)].
It is reported that normal tissues from the cervix of the uterus is placed on a culture plate with their epithelial tissues upward, the epithelial cells initiate to grow spread in the form of a sheet around the tissues after 5 to 7 days in the culture [In Vitro Cell. Div. Biol. Animal, 31, 440-446 (1995)]. This sheet of epithelial cells (referred to hereinafter as "outgrowth") has the property of expanding concentrically around normal tissues.
It is known that besides known differentiation marker genes, stress inducible genes, tumor marker genes etc., unknown genes are specifically expressed at the time of growth arrest of outgrowth derived from normal epithelial cells in the cervix of the human uterus [Journal of Stomatological Society of Japan, 62, 78-93 (1995)], but it is not known that specifically expressed unknown genes inhibit the growth of tumor cells.